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Vaginal atresia is a rare obstructive disease of the reproductive tract. It is characterized by the absence or underdevelopment of the vaginal canal and results in various clinical manifestations. Hysterectomy can physically and mentally burden young female patients with a congenital cervix and complete vaginal atresia. This report presents a case of type II vaginal atresia complicated by cervical dysplasia in a female patient >10 years of age. Our team opted to preserve the patient's uterus, innovated a fallopian tube transplantation technique, and performed cervicovaginal reconstruction using natural channels instead of the cervical canal. The patient experienced menarche within the first 2 weeks postoperatively, and follow-up at 6 months revealed no abnormalities.
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Colo do Útero , Displasia do Colo do Útero , Vagina , Humanos , Feminino , Colo do Útero/anormalidades , Colo do Útero/cirurgia , Colo do Útero/patologia , Vagina/anormalidades , Vagina/cirurgia , Displasia do Colo do Útero/cirurgia , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/patologia , Tubas Uterinas/cirurgia , Tubas Uterinas/anormalidades , Tubas Uterinas/patologia , Anormalidades CongênitasRESUMO
BACKGROUND AND OBJECTIVES: Craniocervical junction (CCJ) arteriovenous fistulas (AVFs) are rare. Variability in clinical manifestations and treatment strategies for CCJ AVFs stems from differences in their angioarchitecture. Our study aims to categorize CCJ AVFs based on their angioarchitecture and explore the associated clinical features and treatment modalities for distinct CCJ AVF types. METHODS: The authors conducted a retrospective analysis of patients with CCJ AVFs treated at a single neurosurgical facility over the past decade. These patients were classified based on the angioarchitecture of their CCJ AVFs. The analysis included an evaluation of angioarchitecture, clinical characteristics, treatment strategies, and outcomes. RESULTS: The study included 155 patients, with a median age of 56 years, collectively manifesting 165 CCJ AVFs. Our classification identified 4 distinct CCJ AVF types: epidural AVFs (19 [11.5%]), dural AVFs (98 [59.4%]), radicular AVFs (33 [20.0%]), and perimedullary AVFs (15 [9.1%]). Further differentiation was applied based on the presence of pial feeders. The predominant fistula location was at cervical-1 (77.0%). Ascending intradural drainage (52.7%) and descending intradural drainage (52.1%) were frequently observed drainage patterns. Patients with dural AVF predominantly presented with venous hypertensive myelopathy, whereas patients with other types of CCJ AVFs showed a higher incidence of subarachnoid hemorrhage (P = .012). Microsurgery was the predominant treatment, applied in the management of 126 (76.4%) AVFs, whereas 8 (4.8%) AVFs exclusively underwent interventional embolization and 25 (15.2%) received a combination of interventional embolization and microsurgical treatment. CONCLUSION: CCJ AVFs can be distinguished based on the fistula location and the arterial feeders. Currently, microsurgery stands as the preferred treatment strategy for CCJ AVFs, whereas interventional embolization plays a distinctive role in cases with specific angioarchitecture or as a pretreatment measure before microsurgery.
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Fístula Arteriovenosa , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Idoso , Estudos Retrospectivos , Fístula Arteriovenosa/cirurgia , Fístula Arteriovenosa/terapia , Fístula Arteriovenosa/diagnóstico por imagem , Estudos de Coortes , Embolização Terapêutica/métodos , Resultado do Tratamento , Adulto Jovem , Adolescente , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Primary carnitine deficiency (PCD) is a rare autosomal recessive fatty acid oxidation disorder caused by variants in SLC22A5, with its prevalence and SLC22A5 gene mutation spectrum varying across races and regions. This study aimed to systematically analyze the incidence of PCD in China and delineate regional differences in the prevalence of PCD and SLC22A5 gene variants. METHODS: PubMed, Embase, Web of Science, and Chinese databases were searched up to November 2023. Following quality assessment and data extraction, a meta-analysis was performed on screening results for PCD among Chinese newborns. RESULTS: After reviewing 1,889 articles, 22 studies involving 9,958,380 newborns and 476 PCD cases were included. Of the 476 patients with PCD, 469 underwent genetic diagnosis, revealing 890 variants of 934 alleles of SLC22A5, among which 107 different variants were detected. The meta-analysis showed that the prevalence of PCD in China was 0.05 [95%CI, (0.04, 0.06)] or 1/20 000 [95%CI, (1/16 667, 1/25 000)]. Subgroup analyses revealed a higher incidence in southern China [0.07, 95%CI, (0.05, 0.08)] than in northern China [0.02, 95%CI, (0.02, 0.03)] (P < 0.001). Furthermore, the result of the meta-analysis showed that the frequency of the variant with c.1400C > G, c.51C > G, c.760C > T, c.338G > A, and c.428C > T were 45% [95%CI, (34%, 59%)], 26% [95%CI, (22%, 31%)], 14% [95%CI, (10%, 20%)], 6% [95%CI, (4%, 8%)], and 5% [95%CI, (4%, 8%)], respectively. Among the subgroup analyses, the variant frequency of c.1400C > G in southern China [39%, 95%CI, (29%, 53%)] was significantly lower than that in northern China [79, 95%CI, (47, 135)] (P < 0.05). CONCLUSIONS: This study systematically analyzed PCD prevalence and identified common SLC22A5 gene variants in the Chinese population. The findings provide valuable epidemiological insights and guidance for future PCD screening effects in newborns.
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Carnitina , Hiperamonemia , Membro 5 da Família 22 de Carreadores de Soluto , Humanos , China/epidemiologia , Carnitina/deficiência , Recém-Nascido , Membro 5 da Família 22 de Carreadores de Soluto/genética , Hiperamonemia/genética , Hiperamonemia/epidemiologia , Hiperamonemia/diagnóstico , Cardiomiopatias/genética , Cardiomiopatias/epidemiologia , Doenças Musculares/genética , Doenças Musculares/epidemiologia , Mutação/genética , Triagem Neonatal/métodos , População do Leste AsiáticoRESUMO
OBJECTIVE: Accurate nidus segmentation and quantification have long been challenging but important tasks in the clinical management of Cerebral Arteriovenous Malformation (CAVM). However, there are still dilemmas in nidus segmentation, such as difficulty defining the demarcation of the nidus, observer-dependent variation and time consumption. The aim of this study isto develop an artificial intelligence model to automatically segment the nidus on Time-Of-Flight Magnetic Resonance Angiography (TOF-MRA) images. METHODS: A total of 92patients with CAVM who underwent both TOF-MRA and DSA examinations were enrolled. Two neurosurgeonsmanually segmented the nidusonTOF-MRA images,which were regarded as theground-truth reference. AU-Net-basedAImodelwascreatedfor automatic nidus detectionand segmentationonTOF-MRA images. RESULTS: The meannidus volumes of the AI segmentationmodeland the ground truthwere 5.427 ± 4.996 and 4.824 ± 4.567 mL,respectively. The meandifference in the nidus volume between the two groups was0.603 ± 1.514 mL,which wasnot statisticallysignificant (P = 0.693). The DSC,precision and recallofthe testset were 0.754 ± 0.074, 0.713 ± 0.102 and 0.816 ± 0.098, respectively. The linear correlation coefficient of the nidus volume betweenthesetwo groupswas 0.988, p < 0.001. CONCLUSION: The performance of the AI segmentationmodel is moderate consistent with that of manual segmentation. This AI model has great potential in clinical settings, such as preoperative planning, treatment efficacy evaluation, riskstratification and follow-up.
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Inteligência Artificial , Malformações Arteriovenosas Intracranianas , Angiografia por Ressonância Magnética , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Feminino , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Introduction: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked hereditary disorder in southern China. However, the incidence rate of G6PD deficiency and the frequency of the most common G6PD gene variants vary widely. The purpose of this study was to investigate the prevalence, genotype, and phenotypic features of G6PD deficiency in neonates in Fujian province, southeastern China. Methods: This retrospective cohort study enrolled 2,789,002 newborns (1,521,431 males and 1,267,571 females) based on the newborn screening program for G6PD deficiency in Fujian Province between January 2010 and December 2021. Results: Of the 2,789,002 newborns enrolled, 26,437 cases were diagnosed (22,939 males and 3,498 females), and the estimated prevalence of G6PD deficiency in Fujian province was 0.95%. The prevalence was significantly higher among males (1.51%) than in females (0.28%) (p < 0.00001). Among the 3,198 patients with G6PD deficiency, 3,092 cases (2,145 males and 947 females) were detected to have G6PD gene variants. The top six prevalent genotypes identified represented 90.84% (2095/3,198) of the total and included c.1376G > T (44.93%), c.1388G > A (18.42%), c.1024C > T (9.32%), c.95A > G (8.69%), c.392G > T (5.25%), and c.871G > A (4.22%). The frequency of genotypes with c.1388G > A, c.1024C > T, and c.871G > A was higher in males in the Fujian province than in females, while the frequency of genotypes with c.1376G > T was lower. Furthermore, when comparing the enzyme activities of the top six prevalent genotypes, there were significant differences in the enzyme activities among the genotypes of male hemizygotes and female heterozygotes. According to the new classification of G6PD variants proposed by the World Health Organization (WHO), the variants with c.1376G > T, c.95A > G, and c.871G > A were recognized as Class A, while the c.392G > T, c.1388G > A, and c.1024C > T were recognized as Class B. Discussion: To the best of our knowledge, this study is the first to systematically describe the overview of epidemiological characteristics of newborn G6PD deficiency in Fujian province, China, including the screening rate, incidence rate, and variant spectrum. Additionally, we elucidated the relationship between the distribution of enzyme activity with specific mutations and their WHO classification patterns. Our results could provide strategies for screening, diagnosis, and genetic counseling of G6PD deficiency in this area.
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Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.
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Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Humanos , Animais , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP1A2/efeitos dos fármacosRESUMO
OBJECTIVE: The highly intricate nature of the cervical spinal cord can cause arteriovenous shunts in these segments that may be associated with heightened clinical risks and treatment complexities. In this article, the authors aimed to provide a comprehensive analysis of the detailed natural course, treatment, and clinical outcomes of cervical spinal cord arteriovenous shunts (SCAVSs) based on the largest cohort to date. METHODS: Two hundred forty consecutive patients were included. Data on clinical presentation, angioarchitecture, treatment, and follow-up were retrospectively reviewed. RESULTS: The cohort demonstrated a greater prevalence of acute onset (63.3% vs 36.7%). Spontaneous recovery was observed in 63.7% of patients after onset, with a significantly elevated recovery rate observed among patients experiencing acute onset (72.4% vs 48.9%, p < 0.001). The risks of acute and gradual clinical deterioration after onset was 11.9%/year and 13.4%/year, respectively. Microsurgery was performed in 39.6% of patients, while the remaining 60.4% exclusively underwent embolization. The complete obliteration rate was 65.3% after microsurgery and 21.4% after embolization. The rate of treatment-related deterioration was 14.7% after microsurgery and 6.2% after embolization. After partial treatment, the acute and gradual deterioration rates were 4.1%/year and 6.6%/year, respectively. Lack of spontaneous recovery after onset was an independent predictor of embolization-related deterioration (OR 17.905, p = 0.007) and long-term gradual deterioration after partial treatment (HR 2.325, p = 0.021). After a median follow-up period of 32.55 months, prognosis was unfavorable in 16.7% of patients, with the sole independent risk factor being the absence of spontaneous recovery after onset (OR 2.476, p = 0.018). CONCLUSIONS: The outcomes of patients with cervical SCAVS were generally favorable, even in patients with only partial obliteration of the lesions. However, patients who did not show a trend toward spontaneous recovery after onset had a significantly elevated risk of unfavorable prognosis, highlighting the need for prompt clinical intervention.
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Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.
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Bilirubin-induced brain damage is a serious clinical consequence of hyperbilirubinemia, yet the underlying molecular mechanisms remain largely unknown. Ferroptosis, an iron-dependent cell death, is characterized by iron overload and lipid peroxidation. Here, we report a novel regulatory mechanism of demethylase AlkB homolog 5 (ALKBH5) in acyl-coenzyme A synthetase long-chain family member 4 (ACSL4)-mediated ferroptosis in hyperbilirubinemia. Hyperdifferential PC12 cells and newborn Sprague-Dawley rats were used to establish in vitro and in vivo hyperbilirubinemia models, respectively. Proteomics, coupled with bioinformatics analysis, first suggested the important role of ferroptosis in hyperbilirubinemia-induced brain damage. In vitro experiments showed that ferroptosis is activated in hyperbilirubinemia, and ferroptosis inhibitors (desferrioxamine and ferrostatin-1) treatment effectively alleviates hyperbilirubinemia-induced oxidative damage. Notably, we observed that the ferroptosis in hyperbilirubinemia was regulated by m6A modification through the downregulation of ALKBH5 expression. MeRIP-seq and RIP-seq showed that ALKBH5 may trigger hyperbilirubinemia ferroptosis by stabilizing ACSL4 mRNA via m6A modification. Further, hyperbilirubinemia-induced oxidative damage was alleviated through ACSL4 genetic knockdown or rosiglitazone-mediated chemical repression but was exacerbated by ACSL4 overexpression. Mechanistically, ALKBH5 promotes ACSL4 mRNA stability and ferroptosis by combining the 669 and 2015 m6A modified sites within 3' UTR of ACSL4 mRNA. Our findings unveil a novel molecular mechanism of ferroptosis and suggest that m6A-dependent ferroptosis could be an underlying clinical target for the therapy of hyperbilirubinemia.
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Homólogo AlkB 5 da RNA Desmetilase , Coenzima A Ligases , Ferroptose , Estabilidade de RNA , Ratos Sprague-Dawley , Animais , Ferroptose/genética , Ratos , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/genética , Células PC12 , Cicloexilaminas/farmacologia , Humanos , Desferroxamina/farmacologia , Estresse Oxidativo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/genética , Lesões Encefálicas/patologia , Lesões Encefálicas/etiologia , Fenilenodiaminas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Masculino , Modelos Animais de Doenças , Peroxidação de LipídeosRESUMO
Osteosarcoma (OS) is a rare form of cancer and primary bone malignancy in children and adolescents. Current therapies include surgery, chemotherapy, and amputation. Therefore, a new therapeutic strategy is needed to dramatically change cancer treatment. Recently, chimeric antigen receptor T cells (CAR-T cells) have been of considerable interest as it has provided auspicious results and patients suffering from low side effects after injection that resolve with current therapy. However, there are reports that cytokine release storm (CRS) can be observed in some patients. In addition, as researchers have faced problems that limit and suppress T cells, further studies are required to resolve these problems. In addition, to maximize the therapeutic benefit of CAR-T cell therapy, researchers have suggested that combination therapy could be better used to treat cancer by overcoming any problems and reducing side effects as much as possible. This review summarizes these problems, barriers, and the results of some studies on the evaluation of CAR-T cells in patients with osteosarcoma.
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BACKGROUND: Sepsis is a disease characterized by infection-induced multiorgan dysfunction, which can progress to septic shock if not promptly treated. Early identification of sepsis is crucial for its treatment. However, there are currently limited specific biomarkers for sepsis or septic shock. This study aims to identify potential biomarkers for sepsis and septic shock. METHODS: We analyzed single-cell transcriptomic data of peripheral blood mononuclear cells (PBMCs) from healthy individuals, sepsis and septic shock patients, identified differences in gene expression and cell-cell communication between different cell types during disease progression. Moreover, our analyses were further validated with flow cytometry and bulk RNA-seq data. RESULTS: Our study elucidates the alterations in cellular proportions and cell-cell communication among healthy controls, sepsis, and septic shock patients. We identified a specific augmentation in the Resistin signaling within sepsis monocytes, mediated via RETN-CAP1 ligand-receptor pairs. Additionally, we observed enhanced IL16 signaling within monocytes from septic shock patients, mediated through IL16-CD4 ligand-receptor pairs. Subsequently, we confirmed our findings by validating the increase in CAP-1+ monocytes in sepsis and IL16+ monocytes in septic shock in mouse models. And a significant upregulation of CAP-1 and IL16 was also observed in the bulk RNA-seq data from patients with sepsis and septic shock. Furthermore, we identified four distinct clusters of CD14+ monocytes, highlighting the heterogeneity of monocytes in the progress of sepsis. CONCLUSIONS: In summary, our work demonstrates changes in cell-cell communication of healthy controls, sepsis and septic shock, confirming that the molecules CAP-1 and IL16 on monocytes may serve as potential diagnostic markers for sepsis and septic shock, respectively. These findings provide new insights for early diagnosis and stratified treatment of the disease.
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Biomarcadores , Comunicação Celular , Sepse , Choque Séptico , Análise de Célula Única , Humanos , Choque Séptico/sangue , Choque Séptico/imunologia , Animais , Sepse/imunologia , Sepse/diagnóstico , Sepse/genética , Camundongos , Masculino , Monócitos/imunologia , Monócitos/metabolismo , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/imunologia , Análise de Sequência de RNA , Feminino , Camundongos Endogâmicos C57BL , Pessoa de Meia-IdadeRESUMO
Polymeric micelle systems for drug delivery, monitor and chemotherapy have gained significant attention, and reductive polymeric micelle systems have become particularly attractive due to their controlled release behavior without additional assistance. However, there are challenges in accurately controlling drug and probe release from the nanoparticles and determining the loading content of drug and probe. To address these issues, we have developed a reduction-responsive Pt(IV) prodrug-based polymeric delivery system that can be dynamically monitored using aggregation-induced emission luminogens (AIE) based bioprobes. These polymeric micelle can self-assemble into nanoparticles and release both bio-active Pt(II) drug and bio-probe upon reduction activation. TPE molecules released in the inner endo/lysosomal microenvironment aggregate and fluoresce upon irradiation, thus allowing real-time tracking of drug biodistribution without additional contrast agents. Advantages of this system include position-specific chemical bond cleavage, control of platinum content, and monitoring of drug reduction and biodistribution.
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Nanopartículas , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Micelas , Distribuição Tecidual , Sistemas de Liberação de Medicamentos , Polímeros/química , Nanopartículas/químicaRESUMO
BACKGROUND: Artificial intelligence (AI) has rapidly advanced in the medical field, leveraging its intelligence and automation for the management of various diseases. Brain arteriovenous malformations (AVM) are particularly noteworthy, experiencing rapid development in recent years and yielding remarkable results. This paper aims to summarize the applications of AI in the management of AVMs management. METHODS: Literatures published in PubMed during 1999-2022, discussing AI application in AVMs management were reviewed. RESULTS: AI algorithms have been applied in various aspects of AVM management, particularly in machine learning and deep learning models. Automatic lesion segmentation or delineation is a promising application that can be further developed and verified. Prognosis prediction using machine learning algorithms with radiomic-based analysis is another meaningful application. CONCLUSIONS: AI has been widely used in AVMs management. This article summarizes the current research progress, limitations and future research directions.
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OBJECTIVE: Isolated spinal aneurysms (ISAs) are rare causes of subarachnoid hemorrhage (SAH), which encompass a highly heterogeneous group of clinical entities with multifarious pathogeneses, clinical characteristics, and treatment strategies. Therefore, knowledge about the ISAs remains inadequate. In this study, the authors present a comprehensive analysis of clinical data associated with ISAs at their institutions to enhance the understanding of this disease. METHODS: Patients with ISAs confirmed by spinal angiography or surgery at the authors' institutions between 2015 and 2022 were included. Data regarding clinical presentation, lesion location, aneurysm morphology, comorbidities, treatment results, and clinical outcomes were reviewed. RESULTS: Seven patients with ISAs were included in the study. Among them, 4 patients (57.1%) experienced severe headache, and 3 patients (42.9%) reported sudden-onset back pain. Additionally, lower-extremity weakness and urinary retention were observed in 2 of these patients (28.6%). Four of the aneurysms exhibited fusiform morphology, whereas the remaining were saccular. All saccular aneurysms in this series were attributed to hemodynamic factors. Conservative treatment was administered to 3 patients, 2 of whom underwent follow-up digital subtraction angiography, which showed spontaneous occlusion of both aneurysms. Four patients ultimately underwent invasive treatments, including 2 who underwent microsurgery and 2 who received endovascular embolization. One patient died of recurrent SAH, while the remaining 6 patients had a favorable prognosis at the latest follow-up assessment. CONCLUSIONS: The morphology of aneurysms may be associated with their etiology. Saccular ISAs are usually caused by pressure due to abnormally increased blood flow, whereas fusiform lesions may be more likely to be secondary to vessel wall damage. The authors found that a saccular spinal aneurysm in young patients with a significant dilated parent artery may be a vestige of spinal cord arteriovenous shunts. ISAs can be managed by surgical, endovascular, or conservative procedures, and the clinical outcome is generally favorable. However, the heterogeneous nature of the disease necessitates personalized treatment decision-making based on specific clinical features of each patient.
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Embolização Terapêutica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Resultado do Tratamento , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/cirurgia , Hemorragia Subaracnóidea/terapia , Aneurisma/cirurgia , Aneurisma/etiologia , Aneurisma/diagnóstico por imagem , Estudos Retrospectivos , Microcirurgia , Angiografia Digital , Procedimentos Endovasculares , Medula Espinal/irrigação sanguínea , Medula Espinal/patologiaRESUMO
BACKGROUND AND PURPOSE: Vertebrobasilar dolichoectasia aneurysm is a rare type of cerebrovascular disorder with a poor natural history, and endovascular treatment is widely accepted. Whether a high-profile braided stent (flow diverter) could promote occlusion of vertebrobasilar dolichoectasia aneurysm without increasing the complications rather than a low-profile braided stent remains uncertain. The aim of the study was to present a single-center experience of the safety and efficacy of a low-profile braided stent versus a flow diverter in treating patients with vertebrobasilar dolichoectasia aneurysms. MATERIALS AND METHODS: The retrospective review was conducted on a total of 432 consecutive patients diagnosed with posterior circulation aneurysms who underwent endovascular treatment in our center from August 2013 to December 2021. Among these patients, 47 individuals with vertebrobasilar dolichoectasia aneurysms who were treated with low-profile braided stents or flow diverters were included. Vertebrobasilar dolichoectasia aneurysms involving only the vertebral artery were excluded. Patients were divided into 2 groups: the low-profile braided stent group and the flow diverter group based on the device used. Safety and efficacy outcomes were subsequently analyzed. RESULTS: There were 25 total patients enrolled in low-profile braided stent group and 22 patients in flow diverter group. The safety of low-profile braided stents and flow diverters in the treatment of vertebrobasilar dolichoectasia aneurysms was evaluated by clinical outcome, a new neurologic deficit due to procedural complications, and neurologic death. The rates of good clinical outcome were similar between the 2 groups (low-profile braided stent, 56%, versus flow diverter, 59.1%; P = .831), and the rates of neurologic death were also similar (low-profile braided stent, 12%, versus flow diverter, 9.1%; P = .747). Higher rates of new neurologic deficits due to procedural complications were observed in the flow diverter group, but the difference was not significant (low-profile braided stent, 24%, versus flow diverter, 40.9%; P = .215). The efficacy was evaluated by angiographic occlusion of vertebrobasilar dolichoectasia aneurysms and progression of mass effect resulting from these aneurysms. Significantly higher rates of complete occlusion of vertebrobasilar dolichoectasia aneurysms were shown in the flow diverter group (41.2%; P = .028) than in the low-profile braided stent group (10%). CONCLUSIONS: Both low-profile braided stents and flow diverters have similar high risks in reconstructive techniques in the treatment of vertebrobasilar dolichoectasia aneurysms, while a flow diverter is more effective in promoting complete occlusion of vertebrobasilar dolichoectasia aneurysm than a low-profile braided stent. A flow diverter may be a better alternative for carefully selected patients with vertebrobasilar dolichoectasia aneurysms.
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Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Insuficiência Vertebrobasilar , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Seguimentos , Resultado do Tratamento , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Stents , Insuficiência Vertebrobasilar/complicações , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Although stent-assisted coiling embolization (SAC) has been associated with a higher risk of ischemic and hemorrhagic complications, the use of SAC continues to rise for treating ruptured intracranial aneurysms (RIAs). This study aims to assess the safety and effectiveness of dual antiplatelet therapy (DAPT) in the context of RIAs. METHODS: We conducted a retrospective analysis at a single center, involving patients with aneurysmal subarachnoid hemorrhage (aSAH) between May 1, 2017 and December 31, 2021. Patients were categorized into two groups: the SAC group and the non-SAC (NSC) group. Patients in the SAC group received DAPT. We compared modified Rankin Scale (mRS) score, along with hemorrhagic and ischemic complications, between the two groups to evaluate the safety and efficacy of DAPT for SAC. RESULTS: The study included a total of 541 patients, of whom 38 (7.0%) experienced hemorrhagic complications and 48 (8.9%) developed ischemic complications. Additionally, 99 (18.3%) and 84 (15.5%) had poor clinical outcomes at discharge and 6 months, respectively. However, no statistically significant differences were observed between the two groups. Our analysis revealed that aneurysm location in the posterior circulation was a significant risk factor for an unfavorable prognosis when antiplatelet drugs were used following SAC (p = 0.025). CONCLUSIONS: Administering antiplatelet drugs after SAC for RIAs has demonstrated both safety and effectiveness. However, caution should be exercised when considering this treatment strategy for RIAs located in the posterior circulation due to the potentially elevated risk.
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BACKGROUND: Vertebral-basilar artery dissecting aneurysms (VADAs) are an uncommon phenomenon in all fields of cerebrovascular disease. The flow diverter (FD) can be used as an endoluminal reconstruction device that promotes neointima formation at the aneurysmal neck and preserves the parent artery. To date, imaging examinations such as CT angiography, MR angiography, and DSA are the main methods used to evaluate the vasculature of patients. However, none of these imaging methods can reveal the situation of neointima formation, which is of great importance in evaluating occlusion of VADAs, especially those treated with a FD. METHODS: Three patients were included in the study from August 2018 to January 2019. All patients underwent preprocedural, postprocedural, and follow-up evaluations with high resolution MRI, DSA, and optical coherence tomography (OCT), as well as the formation of intima on the surface of the scaffold at the 6 month follow-up. RESULTS: Preprocedural, postoperative, and follow-up high resolution MRI, DSA, and OCT of all three cases successfully evaluated occlusion of the VADAs and occurrence of in stent stenosis from different views of intravascular angiography and neointima formation. CONCLUSIONS: OCT was feasible and useful to further evaluate VADAs treated with FD from a near pathological perspective, which may contribute toward guiding the duration of antiplatelet medication and early intervention of in stent stenosis.
Assuntos
Dissecção Aórtica , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Dissecação da Artéria Vertebral , Humanos , Resultado do Tratamento , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/cirurgia , Artéria Basilar , Tomografia de Coerência Óptica , Constrição Patológica , Neointima , Angiografia Cerebral , Dissecação da Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/cirurgia , Stents , Embolização Terapêutica/métodos , Seguimentos , Procedimentos Endovasculares/métodosAssuntos
Malformações Vasculares do Sistema Nervoso Central , Neoplasias Meníngeas , Meningioma , Neoplasias da Base do Crânio , Humanos , Meningioma/complicações , Meningioma/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico por imagemRESUMO
BACKGROUND: Craniocervical junction (CCJ) arteriovenous fistulas (AVFs) are rare. The current treatment strategies for AVFs with different angioarchitecture need to be clarified. The present study aimed to analyse the correlation between angioarchitecture and clinical characteristics, share our experience in treating this disease and identify risk factors associated with subarachnoid haemorrhage (SAH) and poor outcomes. METHODS: A total of 198 consecutive patients with CCJ AVFs from our neurosurgical centre were retrospectively reviewed. The patients were grouped according to their clinical manifestations, and their baseline clinical characteristics, angioarchitecture, treatment strategies and outcomes were summarised. RESULTS: The patients' median age was 56 years (IQR 47-62 years). The majority of patients were men with 166 (83.8%) patients. The most common clinical manifestation was SAH (52.0%), followed by venous hypertensive myelopathy (VHM) (45.5%). The most common CCJ AVFs type was dural AVF, with 132 (63.5%) fistulas. The most frequent fistula location was C-1 (68.7%) and dural branch of vertebral artery (70.2%) was the most involved arterial feeders for fistulas. The most common direction of venous drainage was descending intradural drainage (40.9%), followed by ascending intradural drainage (36.5%). Microsurgery was the most common treatment strategy applied for 151 (76.3%) patients, 15 (7.6%) patients were treated with interventional embolisation only, and 27 (13.6%) received both interventional embolisation and microsurgical treatment. The learning curve for microsurgery only was analysed by cumulative summation method, and the turning point was the 70th case, and blood loss in post-group was lower than that in pre-group (p=0.034). At the last follow-up, there were 155 (78.3%) patients with favourable outcomes (modified Rankin Scale(mRS)<3). Age≥56 (OR 2.038, 95% CI 1.039 to 3.998, p=0.038), VHM as the clinical manifestation (OR 4.102, 95% CI 2.108 to 7.982, p<0.001) and pretreatment mRS≥3 (OR 3.127, 95% CI 1.617 to 6.047, p<0.001) were significantly associated with poor outcomes. CONCLUSION: The arterial feeders and direction of the venous drainage were important factors in the clinical presentations. The location of fistula and drainage vein was essential for choosing different treatment strategies. Older age, VHM onset and poor pretreatment functional status predicted poor outcomes.
Assuntos
Fístula Arteriovenosa , Embolização Terapêutica , Hemorragia Subaracnóidea , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , Estudos Retrospectivos , Drenagem , Embolização Terapêutica/efeitos adversosRESUMO
Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function. The deletion gave rise to spontaneous intestinal inflammation by inducing epithelial cell necroptosis. Suppression of the necroptotic pathway with deletion of Mlkl or the RIP1 inhibitor Nec-1 rescued colitis phenotypes. Mechanistically, disruption of nuclear TDP-43 caused excessive R-loop accumulation, which triggered DNA damage and genome instability and thereby induced PARP1 hyperactivation, leading to subsequent NAD+ depletion and ATP loss, consequently activating mitochondrion-dependent necroptosis in intestinal epithelial cells. Importantly, restoration of cellular NAD+ levels with NAD+ or NMN supplementation, as well as suppression of ALKBH7, an α-ketoglutarate dioxygenase in mitochondria, rescued TDP-43 deficiency-induced cell death and intestinal inflammation. Furthermore, TDP-43 protein levels were significantly inversely correlated with γ-H2A.X and p-MLKL levels in clinical IBD samples, suggesting the clinical relevance of TDP-43 deficiency-induced mitochondrion-dependent necroptosis. Taken together, these findings identify a unique pathogenic mechanism that links oxidative stress to intestinal inflammation and provide a potent and valid strategy for IBD intervention.